Identification
NameTalmapimod
Accession NumberDB05412
TypeSmall Molecule
GroupsInvestigational
Description

Talmapimod is the first-generation oral p38 MAP kinase inhibitor developed by Scios. It has shown to be effective to cure inflammatory diseases such as Rheumatoid Arthritis.

Structure
Thumb
SynonymsNot Available
External IDs SCIO-469
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
CategoriesNot Available
UNIIB1E00KQ6NT
CAS number309913-83-5
WeightAverage: 513.004
Monoisotopic: 512.199046758
Chemical FormulaC27H30ClFN4O3
InChI KeyZMELOYOKMZBMRB-DLBZAZTESA-N
InChI
InChI=1S/C27H30ClFN4O3/c1-16-13-33(17(2)12-32(16)14-18-6-8-19(29)9-7-18)26(35)21-10-20-22(25(34)27(36)30(3)4)15-31(5)24(20)11-23(21)28/h6-11,15-17H,12-14H2,1-5H3/t16-,17+/m0/s1
IUPAC Name
2-{6-chloro-5-[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazine-1-carbonyl]-1-methyl-1H-indol-3-yl}-N,N-dimethyl-2-oxoacetamide
SMILES
[H][C@]1(C)CN(C(=O)C2=C(Cl)C=C3N(C)C=C(C(=O)C(=O)N(C)C)C3=C2)[C@]([H])(C)CN1CC1=CC=C(F)C=C1
Pharmacology
Indication

Investigated for use/treatment in pain (acute or chronic) and rheumatoid arthritis.

Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action

SCIO-469 inhibits p38 kinase, a stimulatory modulator of pro-inflammatory factors including tumor necrosis factor-alpha (TNFa), interleukin-1 (IL-1), and cyclooxygenase-2 (COX-2), all of which are known to contribute to both symptoms and disease progression in patients with Rheumatoid Arthritis (RA). Existing protein-based products that antagonize TNFa have been shown to markedly relieve the symptoms and retard the progression of RA. It also has the potential for additional benefits associated with its inhibition of IL-1 and COX-2.

TargetKindPharmacological actionActionsOrganismUniProt ID
Mitogen-activated protein kinase 14ProteinunknownNot AvailableHumanQ16539 details
Tumor necrosis factorProteinunknownNot AvailableHumanP01375 details
Interleukin-1 betaProteinunknownNot AvailableHumanP01584 details
Cytochrome c oxidase subunit 2ProteinunknownNot AvailableHumanP00403 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Vanderkerken K, Medicherla S, Coulton L, De Raeve H, Willems A, Lawson M, Van Camp B, Protter AA, Higgins LS, Menu E, Croucher PI: Inhibition of p38alpha mitogen-activated protein kinase prevents the development of osteolytic bone disease, reduces tumor burden, and increases survival in murine models of multiple myeloma. Cancer Res. 2007 May 15;67(10):4572-7. Epub 2007 May 10. [PubMed:17495322 ]
  2. Nguyen AN, Stebbins EG, Henson M, O'Young G, Choi SJ, Quon D, Damm D, Reddy M, Ma JY, Haghnazari E, Kapoun AM, Medicherla S, Protter A, Schreiner GF, Kurihara N, Anderson J, Roodman GD, Navas TA, Higgins LS: Normalizing the bone marrow microenvironment with p38 inhibitor reduces multiple myeloma cell proliferation and adhesion and suppresses osteoclast formation. Exp Cell Res. 2006 Jun 10;312(10):1909-23. Epub 2006 Apr 4. [PubMed:16600214 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentRheumatoid Arthritis1
2CompletedTreatmentBone Marrow Diseases / Bone Marrow Neoplasms / Hematologic Diseases / Myelodysplastic Syndromes1
2CompletedTreatmentMultiple Myeloma (MM)2
2CompletedTreatmentRheumatoid Arthritis2
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00586 mg/mLALOGPS
logP3.78ALOGPS
logP3.9ChemAxon
logS-4.9ALOGPS
pKa (Strongest Basic)5.95ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area65.86 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity139.25 m3·mol-1ChemAxon
Polarizability54.44 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as indolecarboxamides and derivatives. These are compounds containing a carboxamide group attached to an indole.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassIndoles and derivatives
Direct ParentIndolecarboxamides and derivatives
Alternative Parents2-halobenzoic acids and derivatives / N-alkylindoles / Indoles / Aryl ketones / Benzylamines / Phenylmethylamines / Fluorobenzenes / Aralkylamines / N-alkylpiperazines / Aryl fluorides
SubstituentsIndolecarboxamide derivative / 2-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / N-alkylindole / Indole / Benzylamine / Phenylmethylamine / Aryl ketone / Aralkylamine / Halobenzene
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein serine/threonine kinase activity
Specific Function:
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad r...
Gene Name:
MAPK14
Uniprot ID:
Q16539
Molecular Weight:
41292.885 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Tumor necrosis factor receptor binding
Specific Function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs ...
Gene Name:
TNF
Uniprot ID:
P01375
Molecular Weight:
25644.15 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein domain specific binding
Specific Function:
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells.
Gene Name:
IL1B
Uniprot ID:
P01584
Molecular Weight:
30747.7 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Cytochrome-c oxidase activity
Specific Function:
Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. Subunit 2 transfers the electrons from cytochrome c via its binuclear copper A center to the bimetallic center of the catalytic subunit 1.
Gene Name:
MT-CO2
Uniprot ID:
P00403
Molecular Weight:
25564.73 Da
Drug created on November 18, 2007 11:24 / Updated on June 23, 2017 10:14